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This study aimed at assessing the predictive performance of a target-controlled infusion (TCI) system, which incorporates canine PK-PD models for microemulsion and long-chain triglyceride emulsion (LCT) propofol and at investigating time independency of propofol effect on the observed electroencephalographic approximate entropy (ApEn) in TCI. Using a crossover design with a 7-day washout period, 28 healthy beagle dogs were randomized to receive TCI of both formulations in a stepwise or constant manner. Plasma propofol concentrations and ApEn were measured at preset intervals. Pooled biases, inaccuracies, divergences, and wobbles in pharmacokinetic and pharmacodynamic predictions were 2.1% (95% CI: -0.8 to 4.9), 18.1% (15.6-20.5), 1.9%/h, 7.3% (5.4-9.3), and -0.5% (-2.6 to 1.6), 8.7% (7.3-10.1), 2.5%/h, 6.0% (4.1-7.2) for microemulsion propofol, and -9.3% (-11.6 to -6.9), 20.1% (18.2-22.0), 5.1%/h, 7.6% (6.1-9.1) and 5.6% (4.1-7.1), 8.0% (6.9-9.3), 4.7%/h, 4.1% (3.1-5.1) for LCT propofol. Observed ApEn values over time were statistically not different across all time points in a TCI with constant manner. Canine PK-PD model of microemulsion propofol showed good predictive performances. Propofol effect (ApEn) was time independent as long as time is allowed for equilibration.

Equilibrium moisture content (EMC)/equilibrium relative humidity (ERH) studies pertaining to rice and rice products were reviewed. Methods of determining rice and rice component EMC/ERH data varied, using procedures involving static and dynamic equilibration methods, as well as direct gravimetric methods and indirect ERH-measurement methods. Methods for measuring rice and rice component moisture contents also varied. The Modified Henderson and Modified Chung-Pfost equations were most frequently recommended for predicting the sorption behavior of rice. Among rough rice components, for any given temperature and relative humidity, the EMC of milled and brown rice were consistently the greatest, generally followed by rough rice, bran, and hull. The hysteresis effect was apparent in rice. The magnitude of hysteresis decreased with repeated cycles of drying and rewetting and with increasing temperature. EMC/ERH relationships were affected by rice cultivar, but harvest location was not a significant factor. As such, in order to be most accurate, EMC/ERH equations for each rice cultivar need to be determined.

This study compared the blood concentrations of remifentanil obtained in a previous clinical investigation with the predicted remifentanil concentrations produced by different pharmacokinetic models: a non-linear mixed effects model created by the software NONMEM®; an artificial neural network (ANN) model; a support vector machine (SVM) model; and multi-method ensembles. The ensemble created from the mean of the ANN and the non-linear mixed effects model predictions achieved the smallest error and the highest correlation coefficient. The SVM model produced the highest error and the lowest correlation coefficient. Paired t-tests indicated that there was insufficient evidence that the predicted values of the ANN, SVM and two multi-method ensembles differed from the actual measured values at α = 0.05. The ensemble method combining the ANN and non-linear mixed effects model predictions outperformed either method alone. These results indicated a potential advantage of ensembles in improving the accuracy and reducing the variance of pharmacokinetic models.

Clinical characteristics to predict the development of coronary artery abnormalities (CAA) in Kawasaki disease (KD) were assessed by reviewing medical records of patients diagnosed with KD at Korea University Medical Center from March 2001 to February 2005. Of the 285 patients diagnosed with KD, 19 developed CAA (6.7%). Compared with the CAA(-) group, the CAA(+) group had a longer duration of fever after intravenous gamma-globulin (IVGG) injection (2.4+/-2.9 vs. 1.5+/-1.2 days, p=0.008) and higher C-reactive protein (CRP)(12.3+/-7.8 vs. 8.7+/-7.1 mg/dL, p=0.038). In particular, the CAA(+) group tended to have more than 7 days of fever before IVGG and more than 3 days of fever after IVGG (26.3 vs. 5.3%, p0.001; 26.3 vs. 6.4%, p=0.002). When the IVGG responsiveness was defined by the presence of defervescence within 3 days after IVGG, IVGG-non-responders showed a higher incidence of CAA (22.7 vs. 5.3%, p=0.002). Non-responders had a longer duration of fever after IVGG (5.5+/-1.9 vs. 1.2+/-0.6 days, p0.001) and a significantly increased CRP, AST, ALT and total bilirubin. Multivariate regression analysis for CAA showed that the only factor significantly associated with the development of CAA was total fever that lasted for longer than 8 days (OR=4.052, 95% CI=1.151-14.263, p=0.0293). Conclusively, the most important predictor of CAA in KD is total duration of fever longer than 8 days. Early identification of IVGG non-responders and active therapeutic intervention for fever in KD cases might decrease the incidence of CAA.

Adsorption and desorption experiments were carried out on rough rice and brown rice (Nampyung) at 5, 15, 25, 35, for moisture contents between 8.7 and (db). The method employed was to measure the equilibrium relative humidity (ERH) of air in contact with the grain under static conditions, using an electronic hygrometer The effects of temperature and moisture contents were investigated, and the measured values were fitted to the modified Henderson, the modified Chung-Pfost, the modified Halsey and the modified Oswin model. The ERHs of rough rice and brown rice decreased with an decrease in moisture content and temperature, and the effects of temperature was no significant at moisture content of (db). Equilibrium moisture content (EMC) of brown rice was higher than rough rice at same temperature and relative humidity. Desorption EMC is higher than the adsorption, but there is no significant difference between desorption and adsorption EMC in moisture content near (db) at rough rice and near 9, 21 and (db) at brown rice. The modified Oswin model was the best in describing the adsorption EMC and the modified Chung-Pfost model was the best in describing the adsorption ERH of rough rice. The modified Oswin model was the best in describing the adsorption EMC/ERH of brown rice. The modified Chung-Pfost model was the best in describing the desorption EMC/ERH of rough rice and brown rice.

Taxol has been known to block cell division by stabilizing microtubules with promising anticancer activity. However, taxol has distinct cell cycle-independent effects. Recently, this novel drug has been shown to provide a second signal for murine macrophage activation to tumoricidal activity via L-arginine-dependent nitric oxide (NO) synthesis. To investigate the mechanism of taxol-induced NO synthesis, we evaluated the ability of protein kinase C (PKC) inhibitors such as staurosporine (STSN) or polymyxin B to block taxol-induced effects. Taxol alone had only a small effect, whereas taxol in combination with rIFN-gamma markedly increased NO synthesis in a dose-dependent manner. STSN and polymyxin B decreased NO synthesis, which had been induced by rIFN-gamma plus taxol. Furthermore, prolonged incubation of the cells with phorbol ester, which down-regulates PKC activity, abolished synergistic cooperative effect of taxol with rIFN-gamma on NO synthesis. Synergy between IFN-gamma and taxol was mainly dependent on taxol-induced TNF-alpha secretion because not only the increase of inducible NO synthase (iNOS) gene expression by rIFN-gamma plus taxol was associated with the increased expression of TNF-alpha gene but also taxol-induced NO production was decreased by the treatment of anti-murine TNF-alpha neutralizing Abs. STSN and polymyxin B potently inhibited taxol-induced TNF-alpha secretion and TNF-alpha gene expression as well as iNOS gene expression by rIFN-gamma plus taxol. However, rIFN-gamma plus TNF-alpha-induced NO synthesis was not blocked by STSN or polymyxin B. This result indicates that TNF-alpha-induced signaling for induction of NO synthesis is not dependent on PKC activation, and further suggests that the point at which TNF-alpha acts on the NO synthesis from rIFN-gamma-primed macrophages lies next to the point of PKC activation. In conclusion, the present results strongly suggest that the capacity of taxol to increase NO synthesis from rIFN-gamma-primed macrophages is the result of taxol-induced TNF-alpha secretion via the signal transduction pathway of PKC activation.

The role of protein kinase C (PKC) in the induction of nitric oxide (NO) synthesis in murine peritoneal macrophages was examined. Phorbol ester, a PKC activator, had no effect on NO synthesis by itself, whereas IFN-gamma alone had modest activity. When phorbol ester was used in combination with IFN-gamma, there was a marked cooperative induction of NO synthesis in a dose-dependent manner. This increase in NO synthesis was reflected as increased amount of inducible NO synthase (iNOS) mRNA, as determined by Northern blotting. The optimal effect of phorbol ester was shown at 6 h after treatment with IFN-gamma. Phorbol ester also induced the release of NO to the incubation medium by bacillus Calmette-Guerin-infected peritoneal macrophages. Prolonged incubation of cells with phorbol ester, which down-regulates PKC activity, abolished the synergistic cooperative effect on NO production with IFN-gamma. In addition, such PKC inhibitors as staurosporin or polymyxin B reduced NO production induced by IFN-gamma plus phorbol ester. When the cells were treated with both actinomycin D and phorbol ester after IFN-gamma stimulation, more NO was produced and more iNOS mRNA was expressed than in the cells treated with actinomycin D alone. On the basis of these observations, we conclude that PKC might not be directly involved in the expression of NO synthase, but, instead, might be involved in the stabilization of the iNOS mRNA already expressed by the treatment of IFN-gamma.

This study aimed at assessing the predictive performance of a target-controlled infusion (TCI) system, which incorporates canine PK-PD models for microemulsion and long-chain triglyceride emulsion (LCT) propofol and at investigating time independency of propofol effect on the observed electroencephalographic approximate entropy (ApEn) in TCI. Using a crossover design with a 7-day washout period, 28 healthy beagle dogs were randomized to receive TCI of both formulations in a stepwise or constant manner. Plasma propofol concentrations and ApEn were measured at preset intervals. Pooled biases, inaccuracies, divergences, and wobbles in pharmacokinetic and pharmacodynamic predictions were 2.1% (95% CI: -0.8 to 4.9), 18.1% (15.6-20.5), 1.9%/h, 7.3% (5.4-9.3), and -0.5% (-2.6 to 1.6), 8.7% (7.3-10.1), 2.5%/h, 6.0% (4.1-7.2) for microemulsion propofol, and -9.3% (-11.6 to -6.9), 20.1% (18.2-22.0), 5.1%/h, 7.6% (6.1-9.1) and 5.6% (4.1-7.1), 8.0% (6.9-9.3), 4.7%/h, 4.1% (3.1-5.1) for LCT propofol. Observed ApEn values over time were statistically not different across all time points in a TCI with constant manner. Canine PK-PD model of microemulsion propofol showed good predictive performances. Propofol effect (ApEn) was time independent as long as time is allowed for equilibration.

Microemulsion propofol was developed to eliminate lipid solvent-related adverse events of long-chain triglyceride emulsion (LCT) propofol. We compared dose proportionality, pharmacokinetic and pharmacodynamic characteristics of both formulations.The study was a randomized, two-period and crossover design with 7-day wash-out period. Microemulsion and LCT propofol were administered by zero-order infusion (0.75, 1.00 and 1.25 mg kg(-1) min(-1)) for 20 min in 30 beagle dogs (male/female = 5/5 for each rate). Arterial samples were collected at preset intervals. The electroencephalographic approximate entropy (ApEn) was used as a measure of propofol effect. Dose proportionality, pharmacokinetic and pharmacodynamic bioequivalence were evaluated by non-compartmental analyses. Population analysis was performed using nonlinear mixed effects modelling.Both formulations showed dose proportionality at the applied dose range. The ratios of geometric means of AUC(last) and AUC(inf) between both formulations were acceptable for bioequivalence, whereas that of C(max) was not. The pharmacodynamic bioequivalence was indicated by the arithmetic means of AAC (areas above the ApEn time curves) and E(0) (baseline ApEn)-E(max) (maximally decreased ApEn) between both formulations. The pharmacokinetics of both formulations were best described by three compartment models. Body weight was a significant covariate for V(1) of both formulations and sex for k(21) of microemulsion propofol. The blood-brain equilibration rate constants (k(e0), min(-1)) were 0.476 and 0.696 for microemulsion and LCT propofol respectively.Microemulsion propofol was pharmacodynamically bioequivalent to LCT propofol although pharmacokinetic bioequivalence was incomplete, and demonstrated linear pharmacokinetics at the applied dose ranges.

We investigated the effects of the gallotannin penta-O-galloyl-beta-d-glucose (PGG) on interleukin (IL)-8 gene expression and nuclear factor (NF)-kappaB activation. PGG inhibited IL-8 production and gene expression in human monocytic U937 cells stimulated with phorbol myristate acetate (PMA), as measured by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction analysis, respectively. PGG also inhibited PMA-mediated NF-kappaB activation, as measured by electromobility shift assay. Furthermore, PGG prevented PMA-mediated degradation of the NF-kappaB inhibitory protein I-kappaBalpha, as measured by Western blot analysis. PGG also inhibited both IL-8 production and NF-kappaB activation in the U937 cells stimulated with tumor necrosis factor-alpha. These results suggest that PGG, a major constituent of the root cortex of Paeonia suffruticosa ANDREWS, can inhibit IL-8 gene expression by a mechanism involving its inhibition of NF-kappaB activation, which is dependent on I-kappaBalpha degradation.

Nitric oxide (NO) induces apoptotic cell death in murine RAW 264.7 macrophages. To elucidate the inhibitory effects of protein kinase C (PKC) on NO-induced apoptosis, we generated clones of RAW 264.7 cells that overexpress one of the PKC isoforms and explored the possible interactions between PKC and three structurally related mitogen-activated protein (MAP) kinases in NO actions. Treatment of RAW 264.7 cells with sodium nitroprusside (SNP), a NO-generating agent, activated both c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and p38 kinase, but did not activate extracellular signal-regulated kinase (ERK)-1 and ERK-2. In addition, SNP-induced apoptosis was slightly blocked by the selective p38 kinase inhibitor (SB203580) but not by the MAP/ERK1 kinase inhibitor (PD098059). PKC transfectants (PKC-beta II, -delta, and -eta) showed substantial protection from cell death induced by the exposure to NO donors such as SNP and S-nitrosoglutathione (GSNO). In contrast, in RAW 264.7 parent or in empty vector-transformed cells, these NO donors induced internucleosomal DNA cleavage. Moreover, overexpression of PKC isoforms significantly suppressed SNP-induced JNK/SAPK and p38 kinase activation, but did not affect ERK-1 and -2. We also explored the involvement of CPP32-like protease in the NO-induced apoptosis. Inhibition of CPP32-like protease prevented apoptosis in RAW 264.7 parent cells. In addition, SNP dramatically activated CPP32 in the parent or in empty vector-transformed cells, while slightly activated CPP32 in PKC transfectants. Therefore, we conclude that PKC protects NO-induced apoptotic cell death, presumably nullifying the NO-mediated activation of JNK/SAPK, p38 kinase, and CPP32-like protease in RAW 264.7 macrophages.

To investigate the biological functions of protein kinase C delta (PKC delta) in spermatogenesis.We examined PKC delta transcript in mouse testis by means of in situ hybridization and Northern blotting.In testes of normal mice, signals of PKC delta gene expression were detected specifically at the spermatid stage. The PKC delta gene was weakly expressed in 8-week-old mice and highly expressed by 12 weeks. However, the expression was not detected in testes of germ cell-deficient W/Wv mice even at 12 weeks.Protein kinase C delta gene expression may be controlled by specific developmental processes and PKC delta may play a role in spermatogenesis.

Taxol has been known to block cell division by stabilizing microtubules with promising anticancer activity. However, taxol has distinct cell cycle-independent effects. Recently, this novel drug has been shown to provide a second signal for murine macrophage activation to tumoricidal activity via L-arginine-dependent nitric oxide (NO) synthesis. To investigate the mechanism of taxol-induced NO synthesis, we evaluated the ability of protein kinase C (PKC) inhibitors such as staurosporine (STSN) or polymyxin B to block taxol-induced effects. Taxol alone had only a small effect, whereas taxol in combination with rIFN-gamma markedly increased NO synthesis in a dose-dependent manner. STSN and polymyxin B decreased NO synthesis, which had been induced by rIFN-gamma plus taxol. Furthermore, prolonged incubation of the cells with phorbol ester, which down-regulates PKC activity, abolished synergistic cooperative effect of taxol with rIFN-gamma on NO synthesis. Synergy between IFN-gamma and taxol was mainly dependent on taxol-induced TNF-alpha secretion because not only the increase of inducible NO synthase (iNOS) gene expression by rIFN-gamma plus taxol was associated with the increased expression of TNF-alpha gene but also taxol-induced NO production was decreased by the treatment of anti-murine TNF-alpha neutralizing Abs. STSN and polymyxin B potently inhibited taxol-induced TNF-alpha secretion and TNF-alpha gene expression as well as iNOS gene expression by rIFN-gamma plus taxol. However, rIFN-gamma plus TNF-alpha-induced NO synthesis was not blocked by STSN or polymyxin B. This result indicates that TNF-alpha-induced signaling for induction of NO synthesis is not dependent on PKC activation, and further suggests that the point at which TNF-alpha acts on the NO synthesis from rIFN-gamma-primed macrophages lies next to the point of PKC activation. In conclusion, the present results strongly suggest that the capacity of taxol to increase NO synthesis from rIFN-gamma-primed macrophages is the result of taxol-induced TNF-alpha secretion via the signal transduction pathway of PKC activation.

The role of protein kinase C (PKC) in the induction of nitric oxide (NO) synthesis in murine peritoneal macrophages was examined. Phorbol ester, a PKC activator, had no effect on NO synthesis by itself, whereas IFN-gamma alone had modest activity. When phorbol ester was used in combination with IFN-gamma, there was a marked cooperative induction of NO synthesis in a dose-dependent manner. This increase in NO synthesis was reflected as increased amount of inducible NO synthase (iNOS) mRNA, as determined by Northern blotting. The optimal effect of phorbol ester was shown at 6 h after treatment with IFN-gamma. Phorbol ester also induced the release of NO to the incubation medium by bacillus Calmette-Guerin-infected peritoneal macrophages. Prolonged incubation of cells with phorbol ester, which down-regulates PKC activity, abolished the synergistic cooperative effect on NO production with IFN-gamma. In addition, such PKC inhibitors as staurosporin or polymyxin B reduced NO production induced by IFN-gamma plus phorbol ester. When the cells were treated with both actinomycin D and phorbol ester after IFN-gamma stimulation, more NO was produced and more iNOS mRNA was expressed than in the cells treated with actinomycin D alone. On the basis of these observations, we conclude that PKC might not be directly involved in the expression of NO synthase, but, instead, might be involved in the stabilization of the iNOS mRNA already expressed by the treatment of IFN-gamma.

We have studied the production of nitric oxide (NO) and superoxide by murine peritoneal macrophages during activation. The production of NO was induced by activation of cells with recombinant interferon-gamma (rIFN-gamma) and lipopolysaccharide (LPS). Phorbol 12-myristate 13-acetate (PMA)-induced formation of superoxide also increased during activation. However, NO released by the activated macrophages exerted the inhibitory effect on the superoxide formation in the same cells. This fact is supported by the increased production of superoxide when the cells were treated with NG-monomethyl-L-arginine (NGMMA) in addition to stimulation with rIFN-gamma and LPS. The production of superoxide was also inhibited by treatment with sodium nitroprusside (SPN), which spontaneously released nitric oxide in vitro, and at the same time there was increased adenosine diphosphate (ADP)-ribosylation of 37 kDa proteins of the cytoplasm. The 3-aminobenzamide (3-AB) treatment, which decreased ADP-ribosylation, partially reversed SNP-induced inhibition of superoxide generation in macrophages. The above data provide evidence that NO decreases superoxide formation possibly via ADP-ribosylation.

Background and Aim: HHFNC is a widely used respiratory supportive mode for premature infants because of its relatively ease use and good compliance of infants as an alternative of nCPAP in many NICU. The aim of this study is to assess the clinical effectiveness and safety of a new HHFNC device (RT329 Infant Oxygen Delivery System) compared to nCPAP for neonatal respiratory diseases in preterm infants. Methods: Preterm infants who need respiratory support due to neonatal respiratory disease were supplied by HHFNC (n=35) or nCPAP (n=35). Primary outcomes included the rate of weaning and the rate of failure defined as intubation with mechanical ventilator care within 72 hour. Other outcomes included the duration of these respiratory supports, the improvement of vital signs (heart rate and respiratory rate), FiO2 needed for respiratory stabilization and the rate of complications (localized infection and necrosis, air leak syndrome, etc) after HHFNC or nCPAP. Results: There were no significant differences in demographics of patients. 65.7% (23/35) infants in HHFNC group weaned within 72 hours as compared with 74.3% (26/35) infants in nCPAP group (P=0.438 ). 20% (7/35) infants in HHFNC group were intubated compared with 17.1% (6/35) infants in nCPAP group (P=0.603). There were no significant differences in the duration of these respiratory supports and other outcomes. Conclusions: This study indicates that HHFNC may be used as an effective and safe alternative of nNCPAP in the preterm infants. But well-designed randomized study is necessary for clinical

Comparing Humidified High Flow Nasal Cannula (HHFNC) Versus Nasal Continuous Positive Airway Pressure (NCPAP) as Respiratory Supports after Extubation in Preterm Infants

50 Utility of Rapid B-Type Natriuretic Peptide Assay for Diagnosis of Symptomatic Patent Ductus Arteriosus in Preterm Infants

This analysis compares the effects of contraceptive use and infant and fetal mortality on the pace of fertility in Korea and the Philippines and explores the mediating effects of these intermediate variables on educational differentials in childspacing. For both intervals initiated in a recent period before a sample survey, second, third and higher-order intervals are examined. Transitions within successive segments of interval exposure (qx values) are examined rather than cumulative transitions (1 - lx values). This methodological choice is substantively important because breastfeeding should primarily affect early segments of exposure and because it allows empirical examination of the timing of the effects of other variables such as contraceptive use. Further, this choice allows multivariate analysis within the structure of the life-table perspective. The results show substantial differences in patterns between Korea and the Philippines, indicate clearly the effect of each intermediate variable, and illustrate how educational differentials in fertility are affected by contraception and infant and fetal mortality.

Differences among 4 groups of Korean woman--excess fertility and nonexcess fertility women and, within those 2 groups, women who want and do not want additional children--are studied, based on data from the Korean National Fertility Survey of 1974. It was found that the ratio of Korean women who want additional children to those who do not was 3:7. Women's age and years of marriage were factors closely related to the desire for more children among all the women, but more strikingly in the nonexcess fertility group. This group was also more likely to have modernized characteristics in respect to socioeconomic variables, and less likely to have unmet needs with regard to family planning. Based on the Coomb's preference scale, all of the women showed a slightly more than moderate family size (4.4) and a mild preference for sons. Number of living sons was shown to have an effect on desire for additional children. It was undetermined whether those women who want more children are aware of the need for family planning, since on the whole they do not practice contraception and do not show strong psychological motivation toward adopting it. It appeared that there were strong needs remaining unmet at the time of the survey with respect to these women. If strong son preferences continue among these women, a decrease in Korean fertility can not be expected in the immediate future. (Author's modified)

Characteristics of women using what are generally regarded as less effective, or nonprogram, methods of contraception -- rhythm and coitus interruptus. Data were derived from the 1976 Korean National Fertility and Family Planning Survey. Women who used the nonprogram methods were found to be more often better educated and with some work experience, had more knowledge about various methods of contraception and were better informed about population and family planning through mass media or family planning workers. More than half were satisfied with their method and regarded it as best. They expressed negative attitudes toward program methods largely because of their side effects. The lack of side effects from nonprogram methods was a major reason given for using them. The failure rate for the nonprogram group was 27%, compared to 9% for a group of users of program methods. Most of the resulting pregnancies were terminated by induced abortion: these unwanted pregnancies thus contributed both to higher fertility and raised the incidence of induced abortion. Higher parity differences were observed as well between the time of 1st adoption of contraception and the time of survey among the nonprogram users. Better information on the efficacy and safety of program methods is needed for this group of women, who evidently wish to control their fertility but fail to a great extent to do so. (Author's modified)